Full text data of ADPRHL2
ADPRHL2
(ARH3)
[Confidence: low (only semi-automatic identification from reviews)]
Poly(ADP-ribose) glycohydrolase ARH3; 3.2.1.143 (ADP-ribosylhydrolase 3; [Protein ADP-ribosylarginine] hydrolase-like protein 2; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Poly(ADP-ribose) glycohydrolase ARH3; 3.2.1.143 (ADP-ribosylhydrolase 3; [Protein ADP-ribosylarginine] hydrolase-like protein 2; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9NX46
ID ARHL2_HUMAN Reviewed; 363 AA.
AC Q9NX46; Q53G94; Q6IAB8; Q9BY47;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 108.
DE RecName: Full=Poly(ADP-ribose) glycohydrolase ARH3;
DE EC=3.2.1.143;
DE AltName: Full=ADP-ribosylhydrolase 3;
DE AltName: Full=[Protein ADP-ribosylarginine] hydrolase-like protein 2;
DE Flags: Precursor;
GN Name=ADPRHL2; Synonyms=ARH3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=12070318; DOI=10.1110/ps.0200602;
RA Glowacki G., Braren R., Firner K., Nissen M., Kuehl M., Reche P.,
RA Bazan J.F., Cetkovic-Cvrlje M., Leiter E., Haag F., Koch-Nolte F.;
RT "The family of toxin-related ecto-ADP-ribosyltransferases in humans
RT and the mouse.";
RL Protein Sci. 11:1657-1670(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver cancer;
RA Li Y., Wu T., Xu S., Ren S., Chen Z., Han Z.;
RT "A novel gene expressed in human liver cancer tissue.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LYS-209.
RC TISSUE=Thyroid;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, ENZYME REGULATION,
RP COFACTOR, AND MUTAGENESIS OF 77-ASP--ASP-78; 238-GLU--GLU-239 AND
RP 261-GLU--GLU-262.
RX PubMed=16278211; DOI=10.1074/jbc.M510290200;
RA Oka S., Kato J., Moss J.;
RT "Identification and characterization of a mammalian 39-kDa poly(ADP-
RT ribose) glycohydrolase.";
RL J. Biol. Chem. 281:705-713(2006).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=17991898; DOI=10.1128/MCB.01766-07;
RA Niere M., Kernstock S., Koch-Nolte F., Ziegler M.;
RT "Functional localization of two poly(ADP-ribose)-degrading enzymes to
RT the mitochondrial matrix.";
RL Mol. Cell. Biol. 28:814-824(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=22433848; DOI=10.1074/jbc.M112.349183;
RA Niere M., Mashimo M., Agledal L., Dolle C., Kasamatsu A., Kato J.,
RA Moss J., Ziegler M.;
RT "ADP-ribosylhydrolase 3 (ARH3), not poly(ADP-ribose) glycohydrolase
RT (PARG) isoforms, is responsible for degradation of mitochondrial
RT matrix-associated poly(ADP-ribose).";
RL J. Biol. Chem. 287:16088-16102(2012).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 19-363, AND MUTAGENESIS OF
RP GLU-41; ASP-77; SER-148; TYR-149; ASN-151; HIS-182; ASP-314 AND
RP THR-317.
RX PubMed=17015823; DOI=10.1073/pnas.0606762103;
RA Mueller-Dieckmann C., Kernstock S., Lisurek M., von Kries J.P.,
RA Haag F., Weiss M.S., Koch-Nolte F.;
RT "The structure of human ADP-ribosylhydrolase 3 (ARH3) provides
RT insights into the reversibility of protein ADP-ribosylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:15026-15031(2006).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 19-363, SUBSTRATE-BINDING
RP SITE, AND METAL-BINDING SITES.
RX PubMed=21892188; DOI=10.1038/nature10404;
RA Slade D., Dunstan M.S., Barkauskaite E., Weston R., Lafite P.,
RA Dixon N., Ahel M., Leys D., Ahel I.;
RT "The structure and catalytic mechanism of a poly(ADP-ribose)
RT glycohydrolase.";
RL Nature 477:616-620(2011).
CC -!- FUNCTION: Poly(ADP-ribose) synthesized after DNA damage is only
CC present transiently and is rapidly degraded by poly(ADP-ribose)
CC glycohydrolase. Poly(ADP-ribose) metabolism may be required for
CC maintenance of the normal function of neuronal cells. Generates
CC ADP-ribose from poly-(ADP-ribose), but does not hydrolyze ADP-
CC ribose-arginine, -cysteine, -diphthamide, or -asparagine bonds.
CC Due to catalytic inactivity of PARG mitochondrial isoforms, ARH3
CC is the only PAR hydrolyzing enzyme in mitochondria.
CC -!- CATALYTIC ACTIVITY: Hydrolyzes poly(ADP-D-ribose) at glycosidic
CC (1''-2') linkage of ribose-ribose bond to produce free ADP-D-
CC ribose.
CC -!- COFACTOR: Binds 2 magnesium ions per subunit.
CC -!- ENZYME REGULATION: Activity is enhanced by magnesium.
CC -!- SUBUNIT: Monomer (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Mitochondrion matrix. Nucleus.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Belongs to the ADP-ribosylglycohydrolase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK14922.1; Type=Frameshift; Positions=Several;
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DR EMBL; AJ313333; CAC85940.1; -; Genomic_DNA.
DR EMBL; AJ427295; CAD20316.1; -; mRNA.
DR EMBL; AF212236; AAK14922.1; ALT_FRAME; mRNA.
DR EMBL; AK000453; BAA91174.1; -; mRNA.
DR EMBL; CR457237; CAG33518.1; -; mRNA.
DR EMBL; AK223037; BAD96757.1; -; mRNA.
DR EMBL; AL138787; CAC21453.1; -; Genomic_DNA.
DR EMBL; BC014169; AAH14169.1; -; mRNA.
DR RefSeq; NP_060295.1; NM_017825.2.
DR UniGene; Hs.18021; -.
DR PDB; 2FOZ; X-ray; 1.60 A; A=19-363.
DR PDB; 2FP0; X-ray; 2.05 A; A/B=19-363.
DR PDB; 2G4K; X-ray; 1.82 A; A=18-363.
DR PDBsum; 2FOZ; -.
DR PDBsum; 2FP0; -.
DR PDBsum; 2G4K; -.
DR ProteinModelPortal; Q9NX46; -.
DR SMR; Q9NX46; 19-363.
DR IntAct; Q9NX46; 2.
DR MINT; MINT-1420706; -.
DR STRING; 9606.ENSP00000362273; -.
DR PhosphoSite; Q9NX46; -.
DR DMDM; 74753038; -.
DR PaxDb; Q9NX46; -.
DR PeptideAtlas; Q9NX46; -.
DR PRIDE; Q9NX46; -.
DR Ensembl; ENST00000373178; ENSP00000362273; ENSG00000116863.
DR GeneID; 54936; -.
DR KEGG; hsa:54936; -.
DR UCSC; uc001bzt.3; human.
DR CTD; 54936; -.
DR GeneCards; GC01P036554; -.
DR HGNC; HGNC:21304; ADPRHL2.
DR HPA; HPA027104; -.
DR HPA; HPA027141; -.
DR MIM; 610624; gene.
DR neXtProt; NX_Q9NX46; -.
DR PharmGKB; PA134903576; -.
DR eggNOG; COG1397; -.
DR HOGENOM; HOG000225333; -.
DR HOVERGEN; HBG080863; -.
DR InParanoid; Q9NX46; -.
DR KO; K11687; -.
DR OMA; YKKDPDR; -.
DR OrthoDB; EOG7D2FFB; -.
DR PhylomeDB; Q9NX46; -.
DR BRENDA; 3.2.1.143; 2681.
DR EvolutionaryTrace; Q9NX46; -.
DR GeneWiki; ADPRHL2; -.
DR GenomeRNAi; 54936; -.
DR NextBio; 58054; -.
DR PRO; PR:Q9NX46; -.
DR ArrayExpress; Q9NX46; -.
DR Bgee; Q9NX46; -.
DR CleanEx; HS_ADPRHL2; -.
DR Genevestigator; Q9NX46; -.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004649; F:poly(ADP-ribose) glycohydrolase activity; IEA:UniProtKB-EC.
DR InterPro; IPR005502; Ribosyl_crysJ1.
DR Pfam; PF03747; ADP_ribosyl_GH; 1.
DR SUPFAM; SSF101478; SSF101478; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Hydrolase; Magnesium;
KW Metal-binding; Mitochondrion; Nucleus; Polymorphism;
KW Reference proteome; Transit peptide.
FT TRANSIT 1 27 Mitochondrion (Potential).
FT CHAIN 28 363 Poly(ADP-ribose) glycohydrolase ARH3.
FT /FTId=PRO_0000277613.
FT COMPBIAS 2 10 Poly-Ala.
FT METAL 41 41 Magnesium 2.
FT METAL 76 76 Magnesium 1.
FT METAL 77 77 Magnesium 1.
FT METAL 78 78 Magnesium 1.
FT METAL 314 314 Magnesium 2.
FT METAL 316 316 Magnesium 1.
FT METAL 316 316 Magnesium 2.
FT METAL 317 317 Magnesium 2.
FT BINDING 254 254 Substrate (By similarity).
FT VARIANT 209 209 E -> K (in dbSNP:rs2236387).
FT /FTId=VAR_030579.
FT MUTAGEN 41 41 E->A,Q: Significant loss of activity.
FT MUTAGEN 77 78 DD->NN: Complete loss of activity.
FT MUTAGEN 77 77 D->N: Complete loss of activity.
FT MUTAGEN 148 148 S->A: Complete loss of activity.
FT MUTAGEN 149 149 Y->A: Significant loss of activity.
FT MUTAGEN 151 151 N->A: Partial loss of activity.
FT MUTAGEN 182 182 H->Q: Complete loss of activity.
FT MUTAGEN 238 239 EE->QQ: Slight reduction in activity.
FT MUTAGEN 261 262 EE->QQ: Slight reduction in activity.
FT MUTAGEN 314 314 D->E: Complete loss of activity.
FT MUTAGEN 314 314 D->N: Significant loss of activity.
FT MUTAGEN 317 317 T->A: Complete loss of activity.
FT MUTAGEN 317 317 T->S: Partial loss of activity.
FT CONFLICT 109 109 K -> E (in Ref. 4; CAG33518).
FT HELIX 19 37
FT HELIX 38 40
FT HELIX 48 56
FT HELIX 77 92
FT HELIX 97 110
FT TURN 112 115
FT HELIX 118 127
FT HELIX 137 141
FT TURN 142 146
FT HELIX 152 155
FT HELIX 158 163
FT HELIX 167 179
FT HELIX 185 201
FT HELIX 208 222
FT HELIX 226 234
FT HELIX 241 254
FT STRAND 255 257
FT HELIX 260 267
FT STRAND 270 272
FT HELIX 273 275
FT HELIX 277 286
FT HELIX 300 310
FT HELIX 315 330
FT HELIX 332 334
FT HELIX 337 341
FT HELIX 346 360
SQ SEQUENCE 363 AA; 38947 MW; 5FD99F59F27CD29F CRC64;
MAAAAMAAAA GGGAGAARSL SRFRGCLAGA LLGDCVGSFY EAHDTVDLTS VLRHVQSLEP
DPGTPGSERT EALYYTDDTA MARALVQSLL AKEAFDEVDM AHRFAQEYKK DPDRGYGAGV
VTVFKKLLNP KCRDVFEPAR AQFNGKGSYG NGGAMRVAGI SLAYSSVQDV QKFARLSAQL
THASSLGYNG AILQALAVHL ALQGESSSEH FLKQLLGHME DLEGDAQSVL DARELGMEER
PYSSRLKKIG ELLDQASVTR EEVVSELGNG IAAFESVPTA IYCFLRCMEP DPEIPSAFNS
LQRTLIYSIS LGGDTDTIAT MAGAIAGAYY GMDQVPESWQ QSCEGYEETD ILAQSLHRVF
QKS
//
ID ARHL2_HUMAN Reviewed; 363 AA.
AC Q9NX46; Q53G94; Q6IAB8; Q9BY47;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 108.
DE RecName: Full=Poly(ADP-ribose) glycohydrolase ARH3;
DE EC=3.2.1.143;
DE AltName: Full=ADP-ribosylhydrolase 3;
DE AltName: Full=[Protein ADP-ribosylarginine] hydrolase-like protein 2;
DE Flags: Precursor;
GN Name=ADPRHL2; Synonyms=ARH3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=12070318; DOI=10.1110/ps.0200602;
RA Glowacki G., Braren R., Firner K., Nissen M., Kuehl M., Reche P.,
RA Bazan J.F., Cetkovic-Cvrlje M., Leiter E., Haag F., Koch-Nolte F.;
RT "The family of toxin-related ecto-ADP-ribosyltransferases in humans
RT and the mouse.";
RL Protein Sci. 11:1657-1670(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver cancer;
RA Li Y., Wu T., Xu S., Ren S., Chen Z., Han Z.;
RT "A novel gene expressed in human liver cancer tissue.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LYS-209.
RC TISSUE=Thyroid;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, ENZYME REGULATION,
RP COFACTOR, AND MUTAGENESIS OF 77-ASP--ASP-78; 238-GLU--GLU-239 AND
RP 261-GLU--GLU-262.
RX PubMed=16278211; DOI=10.1074/jbc.M510290200;
RA Oka S., Kato J., Moss J.;
RT "Identification and characterization of a mammalian 39-kDa poly(ADP-
RT ribose) glycohydrolase.";
RL J. Biol. Chem. 281:705-713(2006).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=17991898; DOI=10.1128/MCB.01766-07;
RA Niere M., Kernstock S., Koch-Nolte F., Ziegler M.;
RT "Functional localization of two poly(ADP-ribose)-degrading enzymes to
RT the mitochondrial matrix.";
RL Mol. Cell. Biol. 28:814-824(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=22433848; DOI=10.1074/jbc.M112.349183;
RA Niere M., Mashimo M., Agledal L., Dolle C., Kasamatsu A., Kato J.,
RA Moss J., Ziegler M.;
RT "ADP-ribosylhydrolase 3 (ARH3), not poly(ADP-ribose) glycohydrolase
RT (PARG) isoforms, is responsible for degradation of mitochondrial
RT matrix-associated poly(ADP-ribose).";
RL J. Biol. Chem. 287:16088-16102(2012).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 19-363, AND MUTAGENESIS OF
RP GLU-41; ASP-77; SER-148; TYR-149; ASN-151; HIS-182; ASP-314 AND
RP THR-317.
RX PubMed=17015823; DOI=10.1073/pnas.0606762103;
RA Mueller-Dieckmann C., Kernstock S., Lisurek M., von Kries J.P.,
RA Haag F., Weiss M.S., Koch-Nolte F.;
RT "The structure of human ADP-ribosylhydrolase 3 (ARH3) provides
RT insights into the reversibility of protein ADP-ribosylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:15026-15031(2006).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 19-363, SUBSTRATE-BINDING
RP SITE, AND METAL-BINDING SITES.
RX PubMed=21892188; DOI=10.1038/nature10404;
RA Slade D., Dunstan M.S., Barkauskaite E., Weston R., Lafite P.,
RA Dixon N., Ahel M., Leys D., Ahel I.;
RT "The structure and catalytic mechanism of a poly(ADP-ribose)
RT glycohydrolase.";
RL Nature 477:616-620(2011).
CC -!- FUNCTION: Poly(ADP-ribose) synthesized after DNA damage is only
CC present transiently and is rapidly degraded by poly(ADP-ribose)
CC glycohydrolase. Poly(ADP-ribose) metabolism may be required for
CC maintenance of the normal function of neuronal cells. Generates
CC ADP-ribose from poly-(ADP-ribose), but does not hydrolyze ADP-
CC ribose-arginine, -cysteine, -diphthamide, or -asparagine bonds.
CC Due to catalytic inactivity of PARG mitochondrial isoforms, ARH3
CC is the only PAR hydrolyzing enzyme in mitochondria.
CC -!- CATALYTIC ACTIVITY: Hydrolyzes poly(ADP-D-ribose) at glycosidic
CC (1''-2') linkage of ribose-ribose bond to produce free ADP-D-
CC ribose.
CC -!- COFACTOR: Binds 2 magnesium ions per subunit.
CC -!- ENZYME REGULATION: Activity is enhanced by magnesium.
CC -!- SUBUNIT: Monomer (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Mitochondrion matrix. Nucleus.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Belongs to the ADP-ribosylglycohydrolase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK14922.1; Type=Frameshift; Positions=Several;
CC -----------------------------------------------------------------------
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DR EMBL; AJ313333; CAC85940.1; -; Genomic_DNA.
DR EMBL; AJ427295; CAD20316.1; -; mRNA.
DR EMBL; AF212236; AAK14922.1; ALT_FRAME; mRNA.
DR EMBL; AK000453; BAA91174.1; -; mRNA.
DR EMBL; CR457237; CAG33518.1; -; mRNA.
DR EMBL; AK223037; BAD96757.1; -; mRNA.
DR EMBL; AL138787; CAC21453.1; -; Genomic_DNA.
DR EMBL; BC014169; AAH14169.1; -; mRNA.
DR RefSeq; NP_060295.1; NM_017825.2.
DR UniGene; Hs.18021; -.
DR PDB; 2FOZ; X-ray; 1.60 A; A=19-363.
DR PDB; 2FP0; X-ray; 2.05 A; A/B=19-363.
DR PDB; 2G4K; X-ray; 1.82 A; A=18-363.
DR PDBsum; 2FOZ; -.
DR PDBsum; 2FP0; -.
DR PDBsum; 2G4K; -.
DR ProteinModelPortal; Q9NX46; -.
DR SMR; Q9NX46; 19-363.
DR IntAct; Q9NX46; 2.
DR MINT; MINT-1420706; -.
DR STRING; 9606.ENSP00000362273; -.
DR PhosphoSite; Q9NX46; -.
DR DMDM; 74753038; -.
DR PaxDb; Q9NX46; -.
DR PeptideAtlas; Q9NX46; -.
DR PRIDE; Q9NX46; -.
DR Ensembl; ENST00000373178; ENSP00000362273; ENSG00000116863.
DR GeneID; 54936; -.
DR KEGG; hsa:54936; -.
DR UCSC; uc001bzt.3; human.
DR CTD; 54936; -.
DR GeneCards; GC01P036554; -.
DR HGNC; HGNC:21304; ADPRHL2.
DR HPA; HPA027104; -.
DR HPA; HPA027141; -.
DR MIM; 610624; gene.
DR neXtProt; NX_Q9NX46; -.
DR PharmGKB; PA134903576; -.
DR eggNOG; COG1397; -.
DR HOGENOM; HOG000225333; -.
DR HOVERGEN; HBG080863; -.
DR InParanoid; Q9NX46; -.
DR KO; K11687; -.
DR OMA; YKKDPDR; -.
DR OrthoDB; EOG7D2FFB; -.
DR PhylomeDB; Q9NX46; -.
DR BRENDA; 3.2.1.143; 2681.
DR EvolutionaryTrace; Q9NX46; -.
DR GeneWiki; ADPRHL2; -.
DR GenomeRNAi; 54936; -.
DR NextBio; 58054; -.
DR PRO; PR:Q9NX46; -.
DR ArrayExpress; Q9NX46; -.
DR Bgee; Q9NX46; -.
DR CleanEx; HS_ADPRHL2; -.
DR Genevestigator; Q9NX46; -.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004649; F:poly(ADP-ribose) glycohydrolase activity; IEA:UniProtKB-EC.
DR InterPro; IPR005502; Ribosyl_crysJ1.
DR Pfam; PF03747; ADP_ribosyl_GH; 1.
DR SUPFAM; SSF101478; SSF101478; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Hydrolase; Magnesium;
KW Metal-binding; Mitochondrion; Nucleus; Polymorphism;
KW Reference proteome; Transit peptide.
FT TRANSIT 1 27 Mitochondrion (Potential).
FT CHAIN 28 363 Poly(ADP-ribose) glycohydrolase ARH3.
FT /FTId=PRO_0000277613.
FT COMPBIAS 2 10 Poly-Ala.
FT METAL 41 41 Magnesium 2.
FT METAL 76 76 Magnesium 1.
FT METAL 77 77 Magnesium 1.
FT METAL 78 78 Magnesium 1.
FT METAL 314 314 Magnesium 2.
FT METAL 316 316 Magnesium 1.
FT METAL 316 316 Magnesium 2.
FT METAL 317 317 Magnesium 2.
FT BINDING 254 254 Substrate (By similarity).
FT VARIANT 209 209 E -> K (in dbSNP:rs2236387).
FT /FTId=VAR_030579.
FT MUTAGEN 41 41 E->A,Q: Significant loss of activity.
FT MUTAGEN 77 78 DD->NN: Complete loss of activity.
FT MUTAGEN 77 77 D->N: Complete loss of activity.
FT MUTAGEN 148 148 S->A: Complete loss of activity.
FT MUTAGEN 149 149 Y->A: Significant loss of activity.
FT MUTAGEN 151 151 N->A: Partial loss of activity.
FT MUTAGEN 182 182 H->Q: Complete loss of activity.
FT MUTAGEN 238 239 EE->QQ: Slight reduction in activity.
FT MUTAGEN 261 262 EE->QQ: Slight reduction in activity.
FT MUTAGEN 314 314 D->E: Complete loss of activity.
FT MUTAGEN 314 314 D->N: Significant loss of activity.
FT MUTAGEN 317 317 T->A: Complete loss of activity.
FT MUTAGEN 317 317 T->S: Partial loss of activity.
FT CONFLICT 109 109 K -> E (in Ref. 4; CAG33518).
FT HELIX 19 37
FT HELIX 38 40
FT HELIX 48 56
FT HELIX 77 92
FT HELIX 97 110
FT TURN 112 115
FT HELIX 118 127
FT HELIX 137 141
FT TURN 142 146
FT HELIX 152 155
FT HELIX 158 163
FT HELIX 167 179
FT HELIX 185 201
FT HELIX 208 222
FT HELIX 226 234
FT HELIX 241 254
FT STRAND 255 257
FT HELIX 260 267
FT STRAND 270 272
FT HELIX 273 275
FT HELIX 277 286
FT HELIX 300 310
FT HELIX 315 330
FT HELIX 332 334
FT HELIX 337 341
FT HELIX 346 360
SQ SEQUENCE 363 AA; 38947 MW; 5FD99F59F27CD29F CRC64;
MAAAAMAAAA GGGAGAARSL SRFRGCLAGA LLGDCVGSFY EAHDTVDLTS VLRHVQSLEP
DPGTPGSERT EALYYTDDTA MARALVQSLL AKEAFDEVDM AHRFAQEYKK DPDRGYGAGV
VTVFKKLLNP KCRDVFEPAR AQFNGKGSYG NGGAMRVAGI SLAYSSVQDV QKFARLSAQL
THASSLGYNG AILQALAVHL ALQGESSSEH FLKQLLGHME DLEGDAQSVL DARELGMEER
PYSSRLKKIG ELLDQASVTR EEVVSELGNG IAAFESVPTA IYCFLRCMEP DPEIPSAFNS
LQRTLIYSIS LGGDTDTIAT MAGAIAGAYY GMDQVPESWQ QSCEGYEETD ILAQSLHRVF
QKS
//
MIM
610624
*RECORD*
*FIELD* NO
610624
*FIELD* TI
*610624 ADP-RIBOSYLHYDROLASE-LIKE 2; ADPRHL2
;;ADP-RIBOSYLHYDROLASE 3; ARH3
*FIELD* TX
read more
DESCRIPTION
ADP-ribosylation is a reversible posttranslational modification used to
regulate protein function. ADP-ribosyltransferases (see ART1; 601625)
transfer ADP-ribose from NAD+ to the target protein, and
ADP-ribosylhydrolases, such as ADPRHL2, reverse the reaction (Glowacki
et al., 2002).
CLONING
By database analysis and PCR of brain cDNA libraries, Oka et al. (2006)
cloned mouse and human ADPRHL2, which they called ARH3. The deduced
human protein contains 363 amino acids and is 92% identical to its mouse
homolog. Northern blot analysis of mouse tissues showed ubiquitous
expression of Arh3. Western blot analysis of a human liver carcinoma
cell line detected ARH3 in the cytosolic fraction, but not in nuclei.
Analysis of mouse brain and liver revealed Arh3 in both the cytosolic
and nuclear fractions.
BIOCHEMICAL FEATURES
Mueller-Dieckmann et al. (2006) determined the crystal structure of ARH3
lacking its N-terminal 16 amino acids in the presence and absence of ADP
to 1.6 angstrom resolution. They found that ARH3 assumes an
all-alpha-helical fold, and that 2 magnesium ions are flanked by highly
conserved amino acids in the active-site crevice.
GENE FUNCTION
Oka et al. (2006) found that mouse and human ARH3 degraded
poly(ADP-ribose) covalently linked to PARP (173870), but they were
unable to hydrolyze ADP-ribose-arginine, -cysteine, -diphthamide, or
-asparagine bonds. ARH3 activity was enhanced by MgCl(2+). Mutation of
asp77 and asp78 of ARH3 eliminated ribosylhydrolase activity, but not
binding to ADP ribose.
Mueller-Dieckmann et al. (2006) found that human ARH3 bound free
ADP-ribose with micromolar affinity and efficiently de-ADP-ribosylated
poly- but not mono-ADP-ribosylated proteins. Binding, docking, and
mutagenesis experiments suggested a mode of substrate binding and a
reaction mechanism involving Mg(2+) and critical aspartic acid residues.
MAPPING
By genomic sequence analysis, Glowacki et al. (2002) mapped the ADPRH2
gene to chromosome 1p35.3-p34.1.
*FIELD* RF
1. Glowacki, G.; Braren, R.; Firner, K.; Nissen, M.; Kuhl, M.; Reche,
P.; Bazan, F.; Cetkovic-Cvrlje, M.; Leiter, E.; Haag, F.; Koch-Nolte,
F.: The family of toxin-related ecto-ADP-ribosyltransferases in humans
and the mouse. Protein Sci. 11: 1657-1670, 2002.
2. Mueller-Dieckmann, C.; Kernstock, S.; Lisurek, M.; von Kries, J.
P.; Haag, F.; Weiss, M. S.; Koch-Nolte, F.: The structure of human
ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility
of protein ADP-ribosylation. Proc. Nat. Acad. Sci. 103: 15026-15031,
2006.
3. Oka, S.; Kato, J.; Moss, J.: Identification and characterization
of a mammalian 39-kDa poly(ADP-ribose) glycohydrolase. J. Biol. Chem. 281:
705-713, 2006.
*FIELD* CD
Patricia A. Hartz: 11/30/2006
*FIELD* ED
mgross: 11/30/2006
*RECORD*
*FIELD* NO
610624
*FIELD* TI
*610624 ADP-RIBOSYLHYDROLASE-LIKE 2; ADPRHL2
;;ADP-RIBOSYLHYDROLASE 3; ARH3
*FIELD* TX
read more
DESCRIPTION
ADP-ribosylation is a reversible posttranslational modification used to
regulate protein function. ADP-ribosyltransferases (see ART1; 601625)
transfer ADP-ribose from NAD+ to the target protein, and
ADP-ribosylhydrolases, such as ADPRHL2, reverse the reaction (Glowacki
et al., 2002).
CLONING
By database analysis and PCR of brain cDNA libraries, Oka et al. (2006)
cloned mouse and human ADPRHL2, which they called ARH3. The deduced
human protein contains 363 amino acids and is 92% identical to its mouse
homolog. Northern blot analysis of mouse tissues showed ubiquitous
expression of Arh3. Western blot analysis of a human liver carcinoma
cell line detected ARH3 in the cytosolic fraction, but not in nuclei.
Analysis of mouse brain and liver revealed Arh3 in both the cytosolic
and nuclear fractions.
BIOCHEMICAL FEATURES
Mueller-Dieckmann et al. (2006) determined the crystal structure of ARH3
lacking its N-terminal 16 amino acids in the presence and absence of ADP
to 1.6 angstrom resolution. They found that ARH3 assumes an
all-alpha-helical fold, and that 2 magnesium ions are flanked by highly
conserved amino acids in the active-site crevice.
GENE FUNCTION
Oka et al. (2006) found that mouse and human ARH3 degraded
poly(ADP-ribose) covalently linked to PARP (173870), but they were
unable to hydrolyze ADP-ribose-arginine, -cysteine, -diphthamide, or
-asparagine bonds. ARH3 activity was enhanced by MgCl(2+). Mutation of
asp77 and asp78 of ARH3 eliminated ribosylhydrolase activity, but not
binding to ADP ribose.
Mueller-Dieckmann et al. (2006) found that human ARH3 bound free
ADP-ribose with micromolar affinity and efficiently de-ADP-ribosylated
poly- but not mono-ADP-ribosylated proteins. Binding, docking, and
mutagenesis experiments suggested a mode of substrate binding and a
reaction mechanism involving Mg(2+) and critical aspartic acid residues.
MAPPING
By genomic sequence analysis, Glowacki et al. (2002) mapped the ADPRH2
gene to chromosome 1p35.3-p34.1.
*FIELD* RF
1. Glowacki, G.; Braren, R.; Firner, K.; Nissen, M.; Kuhl, M.; Reche,
P.; Bazan, F.; Cetkovic-Cvrlje, M.; Leiter, E.; Haag, F.; Koch-Nolte,
F.: The family of toxin-related ecto-ADP-ribosyltransferases in humans
and the mouse. Protein Sci. 11: 1657-1670, 2002.
2. Mueller-Dieckmann, C.; Kernstock, S.; Lisurek, M.; von Kries, J.
P.; Haag, F.; Weiss, M. S.; Koch-Nolte, F.: The structure of human
ADP-ribosylhydrolase 3 (ARH3) provides insights into the reversibility
of protein ADP-ribosylation. Proc. Nat. Acad. Sci. 103: 15026-15031,
2006.
3. Oka, S.; Kato, J.; Moss, J.: Identification and characterization
of a mammalian 39-kDa poly(ADP-ribose) glycohydrolase. J. Biol. Chem. 281:
705-713, 2006.
*FIELD* CD
Patricia A. Hartz: 11/30/2006
*FIELD* ED
mgross: 11/30/2006